Metabolism is the process the body uses to get or make energy from proteins, carbohydrates and fats. Cystinosis is a disorder in which the body accumulates the amino acid cystine (a building block of proteins) within cells. Excess cystine forms crystals that can build up and damage cells. These crystals negatively affect various systems in the body, especially the eyes, spleen, liver, bone marrow and kidneys. Cystinosis is an autosomal recessive disorder, caused by mutations of the lysosomal cystine carrier cystinosin, encoded by the CTNS gene (17p13). The concomitant intralysosomal cystine accumulation leads to multi-organ damage, with kidneys being the first affected and later spleen, eyes, liver and bone marrow. Altered mitochondrial oxidative phosphorylation has been demonstrated in animal proximal tubules loaded with cystine dimethyl ester, mimicking cystine accumulation in cystinosis, but has not been confirmed in cells of patients with cystinosis.
Non-alcoholic steatohepatitis (NASH) is a liver disease characterized by macrovesicular steatosis, hepatocyte necrosis, inflammation, Mallory bodies, and fibrosis. NASH is closely associated with the metabolic or insulin resistance syndrome. Oxidative stress is believed to play an important role in pathogenesis of NASH. It is likely involved in the progression of disease from steatosis to NASH and potentially cirrhosis. It has been shown that chronic oxidative stress, generated through the oxidation of cytotoxic free fatty acids, can lead to upregulation of cytokines, induction of the liver cytochrome P450 enzyme 2E1, and depletion of hepatic antioxidant concentration.
Neurodegenerative disorders are a heterogeneous group of diseases of the nervous system, including the brain, spinal cord, and peripheral nerves that have much different aetiology. Many are hereditary; some are secondary to toxic or metabolic processes. Free radicals are highly reactive molecules or chemical species capable of independent existence. Generation of highly Reactive Oxygen Species (ROS) is an integral feature of normal cellular function like mitochondrial respiratory chain, phagocytosis and arachidonic acid metabolism. The release of oxygen free radicals has also been reported during the recovery phases from many pathological noxious stimuli to the cerebral tissues. Some of the neurodegenerative disorders include Alzheimer's disease, Huntington's disease, Parkinson's disease and Lateral sclerosis.
Hypertriglyceridemia is a commonly encountered lipid abnormality frequently associated with other lipid and metabolic derangements. The National Cholesterol Education Program recommends obtaining a fasting lipid panel in adults over the age of 20. The discovery of hypertriglyceridemia should prompt an investigation for secondary causes such as high fat diet, excessive alcohol intake, certain medications, and medical conditions (eg, diabetes mellitus, hypothyroidism). In addition, patients should be evaluated for other components of the metabolic syndrome. These include abdominal obesity, insulin resistance, low high-density lipoprotein (HDL), high triglyceride, and hypertension. Hypertriglyceridemia is classified as primary hypertriglyceridemia when there are no secondary causes identified.
Hypertriglyceridemia is a risk factor for pancreatitis and it accounts for 1 to 4% of cases of acute pancreatitis. Although a few patients can develop pancreatitis with triglyceride levels >500 mg/dL, the risk for pancreatitis does not become clinically significant until levels are >1000 mg/dL. More importantly however, hypertriglyceridemia is typically not an isolated abnormality. It is frequently associated with other lipid abnormalities and the metabolic syndrome (abdominal obesity, insulin resistance, low high-density lipoprotein (HDL), high triglyceride, and hypertension), which are linked to coronary artery disease.
Managing acute pathology of often relies on the addressing underlying pathology and symptoms of the disease. There is currently a need in the art for new compositions to treatment of metabolic conditions such as cystinosis, non-alcoholic Steatohepatitis, hypertriglyceridemia and neurodegenerative disorders.